Toxic Proteins in Neurodegenerative Disease
Abstract
A broad range of neurodegenerative disorders is characterized by neuronal damage that may be caused by toxic, aggregation-prone proteins. As genes are identified for these disorders and cell culture and animal models are developed, it has become clear that a major effect of mutations in these genes is the abnormal processing and accumulation of misfolded protein in neuronal inclusions and plaques. Increased understanding of the cellular mechanisms for disposal of abnormal proteins and of the effects of toxic protein accumulation on neuronal survival may allow the development of rational, effective treatment for these disorders.
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Abnormal aggregation of APP-cleaved Aβ peptide and phospho-Tau highlights substantial deregulation of posttranslational events in AD.
“For example, abnormal aggregation of APP-cleaved Aβ peptide and phospho-Tau highlights substantial deregulation of posttranslational events in AD (Taylor et al., 2002).”
From Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression (2020) · cites this paper as Taylor et al., 2002
Accumulation of toxic protein species can kill neurons, and there is growing evidence that ER stress is an important mechanism driving this neurotoxicity.
“Accumulation of toxic protein species can kill neurons, and there is growing evidence that ER stress is an important mechanism driving this neurotoxicity [395].”
From GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review (2022) · cites this paper as [395]
The buildup of neurotoxic agents causes neuronal damage and death, which can lead to neurological dysfunction including cognitive decline, motor abnormalities, mental disorders, and loss of inhibition.
“The buildup of neurotoxic agents is believed to cause neuronal damage and death, which can ultimately lead to various forms of neurological dysfunction that include cognitive decline, motor abnormalities, mental disorders, and loss of inhibition (Chung et al., 2018; Taylor et al., 2002; Vickers et al., 2009).”
From SYK coordinates neuroprotective microglial responses in neurodegenerative disease (2022) · cites this paper as Taylor et al., 2002
Many neurodegenerative diseases have known causes involving mutations in ubiquitously expressed proteins, yet they follow stereotyped degeneration patterns that selectively affect certain cell subsets, producing disease-specific spatial and temporal patterns.
“Many of these diseases have known causes that involve mutations in ubiquitously expressed proteins134, but they follow stereotyped patterns of degeneration that selectively affect certain cell subsets more severely, resulting in disease-specific spatial and temporal patterns of degeneration135–137 (BOX 1).”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [134]
Nearly every neurodegenerative disorder is marked by accumulation of misfolded proteins within or adjacent to affected neurons and glia.
“This notion is underscored by the fact that nearly every neurodegenerative disorder is marked by the accumulation of misfolded proteins within or adjacent to affected neurons and glia, in spite of heterogeneous clinical and pathological characteristics among these diseases [68,69].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [68]
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Background
- Authors
- Taylor, J. P., Hardy, J., & Fischbeck, K. H.
- Affiliations
- National Institutes of Health (US)
- National Institute of Neurological Disorders and Stroke (US)
- Corresponding author
- Taylor, J. Paul
- Venue
- Science
- Published
- 2002-06-14
- Volume
- 296
- Issue
- 5575
- Pages
- 1991-1995
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2121506107
- Cited by
- 1,251
- References
- 74
- Citations by year
- 2026: 18 · 2025: 42 · 2024: 47 · 2023: 40 · 2022: 47 · 2021: 48 · 2020: 50 · 2019: 47 · 2018: 50 · 2017: 42 · 2016: 46 · 2015: 45 · 2014: 68 · 2013: 50 · 2012: 53
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- neurodegenerative diseases, protein toxins, protein aggregation, protein misfolding, neuronal inclusions, plaque, protein clearance, neuronal survival, pathogenic variants, animal models, cell culture model, treatment development
- MeSH terms
- Alzheimer Disease, Amyotrophic Lateral Sclerosis, Animals, Inclusion Bodies, Humans, Mutation, Neurons, Parkinson Disease, Peptides, Proteins, Prion Diseases, Protein Folding, Neurodegenerative Diseases, Trinucleotide Repeat Expansion, Tauopathies
About these checks
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